Differential Regulation of NK Cell Receptors in Acute Lymphoblastic Leukemia
Cancer immunotherapies are preferred over conventional treatments which are highly cytotoxic to normal cells. Focus has been on T cells but natural killer (NK) cells have equal potential. Concepts in cancer control and influence of sex require further investigation to improve successful mobilization...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/7972039 |
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| author | Le Jie Lee Norfarazieda Hassan Siti Zuleha Idris Suresh Kumar Subbiah Heng Fong Seow Norhafizah Mohtaruddin Kian Meng Chang Raudhawati Osman Hishamshah Mohd Ibrahim Sheila Nathan Maha Abdullah |
| author_facet | Le Jie Lee Norfarazieda Hassan Siti Zuleha Idris Suresh Kumar Subbiah Heng Fong Seow Norhafizah Mohtaruddin Kian Meng Chang Raudhawati Osman Hishamshah Mohd Ibrahim Sheila Nathan Maha Abdullah |
| author_sort | Le Jie Lee |
| collection | DOAJ |
| description | Cancer immunotherapies are preferred over conventional treatments which are highly cytotoxic to normal cells. Focus has been on T cells but natural killer (NK) cells have equal potential. Concepts in cancer control and influence of sex require further investigation to improve successful mobilization of immune cells in cancer patients. Acute lymphoblastic leukemia (ALL) is a hematological malignancy mainly of B cell (B-ALL) and T cell (T-ALL) subtypes. Influence of ALL on NK cell is still unclear. Targeted next-generation sequencing was conducted on 62 activating/inhibitory receptors, ligands, effector, and exhaustion molecules on T-ALL (6 males) and normal controls (NC) (4 males and 4 females). Quantitative PCR (q-PCR) further investigated copy number variation (CNV), methylation index (MI), and mRNA expression of significant genes in T-ALL (14 males), NC (12 males and 12 females), and B-ALL samples (N=12 males and 12 females). Bioinformatics revealed unique variants particularly rs2253849 (T>C) in KLRC1 and rs1141715 (A>G) in KLRC2 only among T-ALL (allele frequency 0.8-1.0). Gene amplification was highest in female B-ALL compared to male B-ALL (KLRC2, KLRC4, and NCR3, p<0.05) and lowest in male T-ALL cumulating in deletion of KLRD1 and CD69. MI was higher in male ALL of both subtypes compared to normal (KIR2DL1-2 and 4 and KIR2DS2 and 4, p<0.05) as well as to female B-ALL (KIR3DL2 and KIR2DS2, p<0.05). mRNA expressions were low. Thus, ALL subtypes potentially regulated NK cell suppression by different mechanisms which should be considered in future immunotherapies for ALL. |
| format | Article |
| id | doaj-art-d729f58fd78b40699791f06076f68d9f |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-d729f58fd78b40699791f06076f68d9f2025-02-03T01:07:36ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/7972039Differential Regulation of NK Cell Receptors in Acute Lymphoblastic LeukemiaLe Jie Lee0Norfarazieda Hassan1Siti Zuleha Idris2Suresh Kumar Subbiah3Heng Fong Seow4Norhafizah Mohtaruddin5Kian Meng Chang6Raudhawati Osman7Hishamshah Mohd Ibrahim8Sheila Nathan9Maha Abdullah10Department of PathologyUPM-MAKNA Cancer Research LaboratoryDepartment of PathologyUPM-MAKNA Cancer Research LaboratoryDepartment of PathologyDepartment of PathologyDepartment of HematologyHematology UnitPediatric DepartmentSchool of Biosciences and BiotechnologyDepartment of PathologyCancer immunotherapies are preferred over conventional treatments which are highly cytotoxic to normal cells. Focus has been on T cells but natural killer (NK) cells have equal potential. Concepts in cancer control and influence of sex require further investigation to improve successful mobilization of immune cells in cancer patients. Acute lymphoblastic leukemia (ALL) is a hematological malignancy mainly of B cell (B-ALL) and T cell (T-ALL) subtypes. Influence of ALL on NK cell is still unclear. Targeted next-generation sequencing was conducted on 62 activating/inhibitory receptors, ligands, effector, and exhaustion molecules on T-ALL (6 males) and normal controls (NC) (4 males and 4 females). Quantitative PCR (q-PCR) further investigated copy number variation (CNV), methylation index (MI), and mRNA expression of significant genes in T-ALL (14 males), NC (12 males and 12 females), and B-ALL samples (N=12 males and 12 females). Bioinformatics revealed unique variants particularly rs2253849 (T>C) in KLRC1 and rs1141715 (A>G) in KLRC2 only among T-ALL (allele frequency 0.8-1.0). Gene amplification was highest in female B-ALL compared to male B-ALL (KLRC2, KLRC4, and NCR3, p<0.05) and lowest in male T-ALL cumulating in deletion of KLRD1 and CD69. MI was higher in male ALL of both subtypes compared to normal (KIR2DL1-2 and 4 and KIR2DS2 and 4, p<0.05) as well as to female B-ALL (KIR3DL2 and KIR2DS2, p<0.05). mRNA expressions were low. Thus, ALL subtypes potentially regulated NK cell suppression by different mechanisms which should be considered in future immunotherapies for ALL.http://dx.doi.org/10.1155/2022/7972039 |
| spellingShingle | Le Jie Lee Norfarazieda Hassan Siti Zuleha Idris Suresh Kumar Subbiah Heng Fong Seow Norhafizah Mohtaruddin Kian Meng Chang Raudhawati Osman Hishamshah Mohd Ibrahim Sheila Nathan Maha Abdullah Differential Regulation of NK Cell Receptors in Acute Lymphoblastic Leukemia Journal of Immunology Research |
| title | Differential Regulation of NK Cell Receptors in Acute Lymphoblastic Leukemia |
| title_full | Differential Regulation of NK Cell Receptors in Acute Lymphoblastic Leukemia |
| title_fullStr | Differential Regulation of NK Cell Receptors in Acute Lymphoblastic Leukemia |
| title_full_unstemmed | Differential Regulation of NK Cell Receptors in Acute Lymphoblastic Leukemia |
| title_short | Differential Regulation of NK Cell Receptors in Acute Lymphoblastic Leukemia |
| title_sort | differential regulation of nk cell receptors in acute lymphoblastic leukemia |
| url | http://dx.doi.org/10.1155/2022/7972039 |
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